Specific Activation of Human Peripheral Blood γ/δ+ T Lymphocytes by Sonicated Antigens of Mycobacterium tuberculosis: Role In Vitro in Killing Human Bladder Carcinoma Cell Lines

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Abstract
Tumour regression induced in cancer patients by local instillation of Bacillus Calmette-Guérin (BCG) into the bladder has been considered to be mainly mediated by activated cellular immunity and inflammatory reactions. In the present study we investigated the cytotoxicity of T cells bearing gamma/delta T-cell receptors (gamma/delta + cells) against bladder carcinoma cells in vitro. Long-term cultured gamma/delta + T-cell lines from peripheral blood lymphocytes of healthy donors were established by stimulation with sonicated cell wall-associated antigens of Mycobacterium tuberculosis (SMA). These gamma/delta + T cells lack the natural killer (NK) markers CD16 and CD56, as determined by flow cytometry. The SMA-specific gamma/delta + T cells exhibited profound cytotoxicity against two NK-resistant bladder tumour cell lines as well as against NK-sensitive tumour cells in a non-major histocompatibility complex-restricted manner. The pattern of tumour cells killed by gamma/delta + T cells differed significantly from those of NK cells and lymphokine-activated killer LAK cells. Furthermore, we tested the effects of recombinant human cytokines, including interleukin (IL)-1, IL-2, IL-4, IL-6, interferon (IFN)-gamma and tumour necrosis factor (TNF), on gamma/delta + T-cell-mediated cytotoxicity. It was shown that the addition of recombinant TNF in co-incubation could augment gamma/delta + T-cell-mediated killing of two bladder tumour cell lines, but not of cells of the erythroleukaemia cell line K562. Based on these results it was concluded that mycobacterial antigens could specifically activate resting gamma/delta + T cells. The cytotoxicity of gamma/delta + T cells against bladder tumour cells and its selective enhancement by TNF may be an important mechanism involved in bladder tumour regression induced by intravesical instillation of BCG.

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